Neuroendocrinology and Physiology Lab
Our overall research focus is to understand the mechanisms by which long range signaling molecules, e.g. neuropeptides and peptide hormones, act as systemic mediators of intercellular communication to direct critical actions in development, metabolism, reproduction and physiology.
We are interested in the endocrine control of adult organs: what are the molecular, cellular and network mechanisms underpinning the functions of specialized organs and how are these regulated by extrinsic signals in response to internal or external challenges. We typically use Drosophila melanogaster or Tribolium castaneum to explore these questions, as they allow us to explore organ communication from an integrative perspective: how different organs (brain, gut, fat body and kidneys) sense and integrate internal and external signals and relay this information to other organs in a manner that ensures a coordinated response by the organism. Our work is highly cross-disciplinary and typically involve a combination of genome editing and/or genetically encoded tools, cutting-edge ‘omics’ technologies, biochemical methods and classic physiological approaches. Beyond gaining insights into the basic underlying biology, our research may important for understanding human metabolic or kidney disorders and for developing novel insect pest control agents.
Neuroendocrine Targets for Novel Insect Pest Control
Insects are among the most successful organisms on earth, exploiting and inhabiting the widest possible range of habitats. They also pose the biggest threat to global food security, destroying 15-25% of the total crop yields annually. In this project we seek to explore fundamental question in insect physiology and endocrinology to unmask novel targets for insect biocontrol. Using the red flour beetle, Tribolium castaneum, we are exploring mechanisms of ion and water homeostasis (an attractive target for intervention) to identify and characterize neuroendocrine systems involved in regulating salt and water balance. Recent, our work has uncovered a key neuropeptide system that controls beetle ion and water homeostasis by fundamentally different mechanism than other insects (Koyama et al. 2021 PNAS). This study may help guide the development of novel peptide mimetics that can fatally disrupt this critical life processes.
Novel Mechanisms of Osmosensation and Systemic Osmoregulation
Animals must continuously adapt to osmotic challenges to maintain homeostasis and to survive. This requires the coordinated actions of organs with specialized functions, which in turn are modulated by systemic signals communicated by other organs to ensure an appropriate physiological response by the organisms. Molecular osmoreceptors lie at the heart of the central mechanisms coordinating these processes. Yet, the molecular identity of such osmosensitive molecules, and how they modulate the release of known neuroendocrine factors that control systemic osmoregulation, is unknown. Using Drosophila melanogaster for discovery, we aim to gain insights into the molecular, cellular and network mechanisms that control systemic osmoregulation in higher organisms.
Endocrine regulators of AKH/glucagon mediated energy homeostasis
Maintaining biological functions under fluctuating internal and environmental conditions requires the homeostatic control of circulating energy levels. Analogous to mammalian glucagon, the insect adipokinetic hormone (AKH) act as the key hormone in controlling the mobilization of energy reserves during periods of negative energy balance. However, virtually nothing is known about the mechanisms that regulate AKH production and release. We and other have recently shown that the AKH-producing cells are regulated by other systemic factors (Koyama et al. 2021 Nat Comm) raising the possibility that AKH release is under complex control by other extrinsic factors. Using Drosophila genetics in combination with advanced transcriptomic approaches, we aim to gain an authoritative overview of the hormonal pathways that regulate AKH release, which is key to better understand insect metabolism, and more broadly, mechanistic aspects of glycemic control in mammals.
Cell and molecular architecture of a countercurrent exchange system
The insect cryptonephredial complex (CNC) is one of the most powerful water-extraction systems in nature. The essential ‘design principles’ of the CNC lie in the anatomical arrangement of the renal (Malpighian) tubules relative to the rectal epithelia, and on the transport properties of their constituent cells. In effect, the renal tubules build and maintain an osmotic gradient along the length of the rectum allowing the animal extract all water from their excreta to minimize water loss. In some desert species, this mechanism is so efficient that it allows the animal to extract water directly from moist air! In this project, we use Tribolium castaneum as a model to uncover the cellular and molecular architecture underpinning the water reabsorption mechanisms of the CNC. A detailed understanding of CNC function may help inspire biomimicry engineers to design more efficient countercurrent exchange systems, which are broadly used in industry.
Bananfluers tis gør forskere klogere på menneskets tarme
Hvorfor nogle mennesker rammes af tarmsygdommen Cøliaki, som er forbundet til glutenallergi, er endnu uvist. Men bananfluers urin kan netop have bragt forskerne tættere på at forstå, hvorfor sygdommen opstår.
A Unique Renal Architecture in Tribolium castaneum Informs the Evolutionary Origins of Systemic Osmoregulation in Beetles. Koyama T., Naseem M.T., Kolosov D., Vo C.T., Mahon D., Jakobsen A.S.S., Jensen R.L., Denholm B., O’Donnell M., Halberg K.A. PNAS (in press). bioRxiv 2020.11.19.389874; doi: https://doi.org/10.1101/2020.11.19.389874
A nutrient-responsive hormonal circuit controls energy and water homeostasis in Drosophila. Koyama T., Terhzaz S., Naseem M.T., Nagy S., Rewitz K., Dow J.A.T., Davies S.-A., Halberg, K.A. Nature Communications (in review). bioRxiv 2020.07.24.219592; doi: https://doi.org/10.1101/2020.07.24.219592
The gut hormone Allatostatin C regulates food intake and metabolic homeostasis under nutrient stress. Kubrak O., Jensen L., Ahrentløv N., Koyama T., Malita A., Naseem M.T., Lassen M., Nagy S., Texada M.J., Halberg K.A., Rewitz K. Nature Communications (in review). bioRxiv 2020.12.05.412874; doi: https://doi.org/10.1101/2020.12.05.412874
The septate junction protein Snakeskin is critical for epithelial barrier function and tissue homeostasis in the Malpighian tubules of adult Drosophila. A.J. Dornan, K.A. Halberg, L.-K. Beuter, S.-A. Davies, J.A.T. Dow. eLife (in review). bioRxiv 2020.12.14.422678; doi: https://doi.org/10.1101/2020.12.14.422678
Metabolism and growth adaptation to environmental conditions. Koyama, T., Texada, M., Halberg, K.A., Rewitz, K. Cellular and Molecular Life Sciences 77, 4523–4551(2020)
A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion. Texada, M., Joergensen, A.F., Christensen, C.F. Koyama, T., Malita, A., Smith, D., Marple, D.F.M., Danielsen, T., Petersen, S.K. Hansen, J., Halberg, K.A., Rewitz, K. Nature Communications 10:1955 (2019).
Autophagy-mediated cholesterol trafficking controls steroid production. Texada, M., Malita, A., Christensen, C.F., Dall, K.B. Faergeman, N.J. Nagy, S., Halberg, K.A., Rewitz, K. Developmental Cell. 48: 1-13 (2019).
Drosophila as a model for neuroendocrine control for renal homeostasis. Dow J.A.T., Halberg K.A., Terhzaz S., Davies S. In: Model animals in neuroendocrinology: from worm to mouse to man. p. 81-100.
The cell adhesion molecule Fasciclin 2 regulates brush border length and organization in Drosophila renal tubules. Halberg, K. A., Rainy, S., Veland, I. R., Dornan, A. T., Davies, S. & Dow, J. A. T. Nature Communications 7:11266 1-10 (2016).
Tracing the evolutionary origins of insect renal function. Halberg, K. A., Terhzaz, S., Cabrero, P., Davies, S. A. & Dow, J. A. T. Nature Communications 6:6800 1-10 (2015).
- Senior Lecturer Barry Denholm, Centre for Discovery Brain Sciences, University of Edinburgh, UK
- Professor Julian Dow, Institute of Molecular Cell and Systems Biology, University of Glasgow, UK
- Professor Michael O’Donnell, Department of Biology, McMaster University, Canada
- Professor Emeritus David Leader, Institute of Molecular Cell and Systems Biology, University of Glasgow, UK
- Associate Professor, Kirstine Callø, Department of Veterinary and Animal Sciences, University of Copenhagen, DK
- Professor Dan A. Klærke, Department of Veterinary and Animal Sciences, University of Copenhagen, DK
- Professor Kim F. Rewitz, Department of Biology, University of Copenhagen, DK
- Professor Michael F. Romero, Department of Internal Medicine, Mayo Clinic, US
Principal subject on molecular biology and immunology
Basic cell biology